Treatment of Immune-related Adverse Events Refractory to Standard Therapy and Associated Changes in Immunophenotype

Recruiting

• Conditions: Immune-related Adverse Event
• Interventions: Other: Extracorporeal photopheresis; Other: Other immunosuppressive or immunomodulatory drugs

• Registration Number: NCT05700565
• Lead Sponsor: Lucie Heinzerling

Brief Summary

This study is an open, monocentric study. It includes patients with irAE refractory to standard therapy or patients where corticosteroids cannot be tapered. Patients will either be treated with ECP or second line immunosuppressive therapy according to investigator's choice. Patients will be followed for 24 weeks after first treatment.

Detailed Description

At inclusion patient history including type of tumor and immunotherapy will be obtained.

At all visits symptoms, changes in concomitant medication, a medical assessment and laboratory investigations will be performed. Blood sampling for safety analysis and for investigating the immunophenotype will be performed at baseline, week 1, 4, 8 and 12.

Laboratory values assessed include:

* Complete blood count

* Chemistry including liver enzymes (AST, ALT) and total bilirubin in the case of immune-related hepatitis, CK in case of myositis, creatinine in case of nephritis

* Inflammatory markers: CRP, IL-6, Procalcitonin Peripheral blood mononuclear cells (PBMC) will be used to determine immunophenotype, including the amount of NK-cells, regulatory T- cells and myeloid-derived suppressor cells (MDSC) as well as the expression of inflammatory markers. Biological samples will be frozen for later analysis.

Additionally, patients will assess their symptoms and their quality of life by a self-administered questionnaire at baseline and week 4, 8 and 12. Quality of life will be assessed by EORTC QLQ-C30. All irAE will be graded according to CTCAE.

Study Timeline

• Study Start: 2022-01-01
• Study First Submitted: 2022-11-04
• Study First Submitted QC: 2023-01-17
• Study First Posted: 2023-01-26
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-13
• Last Update Posted: 2024-03-15
• Primary Completion: 2027-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Subjects must we willing and able to comply with scheduled visits and must have given written informed consent.
2. irAE after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade)
3. irAE refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent <= 5mg. An irAE is defined as refractory if corticosteroids do not improve symptoms within 72 hours. The inability to taper corticosteroids is defined as relapse on standard tapering of 1 mg/kg corticosteroid over 28 days.

Exclusion Criteria

1. Contraindications for the treatment with ECP including a known sensitivity to psoralen compounds such as 8-MOP, comorbidities that may result in photosensitivity, aphakia, history of heparin-induced thrombocytopenia, unsatisfactory cardio-circulatory function, low hematocrit values
2. Pregnancy
3. Body weight less than 40 kg.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Steroid-refractory or dependent immune-related adverse events	Other immunosuppressive or immunomodulatory drugs	Immune-related adverse events (irAE) after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade) refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent \<= 5mg
Steroid-refractory or dependent immune-related adverse events	Extracorporeal photopheresis	Immune-related adverse events (irAE) after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade) refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent \<= 5mg

Primary Outcome Measures

Name	Time	Method
Immunophenotype	12 weeks	Characterisation of peripheral mononuclear blood cells

Secondary Outcome Measures

Name	Time	Method
Developement of grade of irAE	12 weeks	irAE symptoms graded according to CTCAE v5.0
Patient quality of life	12 weeks	Quality of life assessed by EORTC QLQ-C30

Trial Locations

Locations (1)

LMU Klinikum Hauttumorzentrum; 🇩🇪 Munich, Germany